The field of biotechnology has grown tremendously in the last 20 years. This growth has been due to many factors, some of which include the improvements in the equipment available for bioreactors, the increased understanding of biological systems and increased knowledge as to the interactions of materials (such as monoclonal antibodies and recombinant proteins) with the various systems of the human body.
A perfusion bioreactor processes a continuous supply of fresh media that is fed into the bioreactor while growth-inhibiting byproducts are constantly removed. The nonproductive downtime can be reduced or eliminated with a perfusion bioreactor process. The cell densities achieved in perfusion culture (30-100 million cells/mL) are typically higher than for fed-batch modes (5-25 million cells/mL). These improvements have led to lower contamination in the harvest and better yields without significant increase in cost. A perfusion bioreactor may use a cell retention device to prevent escape of the culture when byproducts are being removed. These cell retention systems may add a level of complexity to the perfusion process, where further management, control, and/or maintenance operations may be implemented. Operational issues such as malfunction or failure of the cell retention equipment has previously been a problem with perfusion bioreactors, which has limited their attractiveness in the past.
In the biotechnology and biopharma fields, it is desirable to separate many different types of materials from a primary fluid stream based on size, surface active materials, density, and other characteristics. Tangential flow filtration has been widely adopted to separate and concentrate diverse array of microbes and other materials from a fluid stream. These materials have been filtered utilizing different physical polymer membranes such as polyvinylidene difluoride (PDF) and polyether sulfone (PES).
Issues that arise with tangential flow filtration include the cost of the membrane materials, the formation of a gel layer or filtrate-suppressing layer on the filter membranes, the consistency of the polymer membranes, and the entire efficiency of the process. There is also the possibility of product loss due to clogging of the polymer membranes and the need to replace these clogged membranes.
There is therefore a need to improve the continuous processing of materials throughout the tangential flow process, decrease the cost, increase the efficiency, and improve the overall ability of the separation process to perform primary, secondary, tertiary and beyond separation of materials from a primary fluid stream.